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Record W3169569927 · doi:10.1101/2021.06.03.446992

<i>Panx1</i> channels promote both anti- and pro-seizure-like activities in the zebrafish via <i>p2rx7</i> receptors and ATP signaling

2021· preprint· en· W3169569927 on OpenAlexafffund
Paige Whyte‐Fagundes, Daria Taskina, Nickie Safarian, Christiane Zoidl, Peter L. Carlen, Logan W. Donaldson, Georg Zoidl

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2021
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicConnexins and lens biology
Canadian institutionsUniversity of TorontoYork UniversityUniversity Health Network
FundersNatural Sciences and Engineering Research Council of CanadaUniversity of Toronto
KeywordsZebrafishNeurosciencePurinergic receptorBiologyEpileptogenesisPannexinPentylenetetrazolEpilepsyCell biologyReceptorPharmacologyAnticonvulsantGeneGenetics

Abstract

fetched live from OpenAlex

Abstract The molecular mechanisms of excitation-inhibition imbalances promoting seizure generation in epilepsy patients are not fully understood. Experimental evidence suggests that Pannexin1 ( Panx1 ), an ATP release channel, modulates excitability of the brain. In this report, we have performed behavioral and molecular phenotyping experiments on zebrafish larvae bearing genetic or pharmacological knockouts of panx1a or panx1b channels, each highly homologous to human PANX1. When Panx1a function is lost or both channels are under pharmacological blockage, treatment with pentylenetetrazol to induce seizures causes reduced ictal-like events and seizure-like locomotion. These observations were extended by transcriptome profiling, where a spectrum of distinct metabolic and cell signaling states correlates with the loss of panx1a . The pro- and anticonvulsant activities of both Panx1 channels affects ATP release and involves the purinergic receptor p2rx7 . We propose that Panx1 zebrafish models offer opportunities to explore the molecular and physiological basis of seizures and assist anticonvulsant drug discovery.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.010
GPT teacher head0.208
Teacher spread0.198 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2021
Admission routes2
Has abstractyes

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Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicConnexins and lens biologyFrench-language works237,207